In vitro test to confirm diagnosis of allopurinol-induced severe cutaneous adverse reactions.

Background Allopurinol is a frequent cause of severe cutaneous adverse reactions ( SCARs), such as drug reaction with eosinophilia and systemic symptoms ( DRESS), Stevens-Johnson syndrome ( SJS) and toxic epidermal necrolysis ( TEN). The reactions can potentially be fatal. As drug rechallenge in patients with a history of drug-induced SCARs is contraindicated, in vitro testing may have a diagnostic role as a confirmation test. Objectives To study the diagnostic value of interferon ( IFN)-γ enzyme-linked immunospot ( ELISpot) assay as a confirmatory test in patients with a history of allopurinol-induced SCARs. Methods Peripheral blood mononuclear cells ( PBMCs) from 24 patients with a history of allopurinol-induced SCAR (13 DRESS, 11 SJS/ TEN) and 21 control subjects were incubated with allopurinol or oxypurinol in the presence or absence of antiprogrammed death ligand 1 antibody (anti- PD-L1). The numbers of IFN-γ-releasing cells after stimulation in each group were subsequently measured with ELISpot. Results The numbers of IFN-γ-releasing cells in allopurinol-allergic subjects were significantly higher than in control subjects when stimulating PBMCs with oxypurinol 100 μg mL⁻¹, especially when adding anti- PD-L1 supplementation. According to the receiver operating characteristic curve results, the optimal discriminatory power of IFN-γ ELISpot in confirming diagnosis of allopurinol-induced SCARs can be obtained using 16 spot-forming cells per 10⁶ PBMCs as a cut-off value upon oxypurinol/anti- PD-L1 stimulation (79·2% sensitivity and 95·2% specificity). Conclusions The measurement of oxypurinol/anti- PD-L1-inducing IFN-γ-releasing cells yields a high diagnostic value in distinguishing between allopurinol-allergic and control subjects. This technique is beneficial in confirming diagnosis of allopurinol-induced SCARs in patients whose reaction develops while taking multiple drugs. [ABSTRACT FROM AUTHOR]